Stent with channel(s) for containing and delivering biologically active material and method for manufacturing the same

ABSTRACT

The invention is directed to an implantable stent prosthesis comprising a sidewall and at least one channel for containing a biologically active material. A method for making such stent prosthesis is also disclosed. In the method, at least one tube or mandrel is placed in contact with a covering material on a stent and surrounded by the covering material to form a channel. Alternatively, a channel can be formed by covering the tube or mandrel with a channel material and exposing the covered tube or mandrel to an appropriate treatment. The channel can be attached to a sidewall of a stent or attached to a strut material to form a stent wire. A method of treating an afflicted area of a body lumen by implanting the stent prosthesis is also disclosed.

[0001] This application is a continuation of U.S. application Ser. No.09/774,218, filed Jan. 30, 2001.

FIELD OF THE INVENTION

[0002] This invention relates generally to an implantable medical devicefor delivering biologically active materials. More specifically, theinvention relates to an implantable stent prosthesis for delivering abiologically active material and a method for manufacturing the same.More particularly, the invention is directed to a stent having one ormore channels for containing and delivering a biologically activematerial.

BACKGROUND OF THE INVENTION

[0003] Balloon angioplasty has been very effective in treating stenosis,i.e., to open blocked vessels and restore normal levels of blood flow.However, although once a blocked vessel is opened, the treated vesselhas a tendency to restenose, i.e., reclose, shortly after the procedure.Thus, patients have to repeatedly be treated with angioplasty orsurgery.

[0004] Implantable stent prosthesis or stents are used to reducerestenosis after balloon angioplasty or other procedures usingcatheters. A stent in the form of a wire mesh tube props open an arterythat has recently been cleared using angioplasty. The stent is collapsedto a small diameter, placed over an angioplasty balloon catheter andmoved into the area of the blockage. When the balloon is inflated, thestent expands, locks in place and forms a scaffold to hold the arteryopen. Usually, the stent stays in the artery permanently, holds it open,improves blood flow to the heart muscle and relieves symptoms. The stentprocedure is fairly common, and various types of stents have beendeveloped and actually used.

[0005] However, the metal surfaces of stents currently in use maytrigger restenosis. To prevent the stented arteries from reclosing,patients who receive stents must take one or more anticoagulating drugs,such as heparin, aspirin, coumadin, dextran, and/or persantine eventhough systemic application of anticoagulants has been known to causebleeding complications.

[0006] To reduce the likelihood of restenosis caused by the metalsurface of such stents, stents covered with polymers and a drug havebeen offered. However, those covered stents are still not completelysatisfactory. Therefore, there is a need for additional devices ormethods to reduce the necessity for systemic application ofanticoagulants and alleviate restenosis.

[0007] Further, for certain diseases which are localized to a particularpart of body, the systemic administration of a biologically activematerial for the treatment of these diseases may not be preferredbecause of the inefficiencies associated with the indirect delivery ofthe biologically active material to the afflicted area. Therefore, thereis a need for a device or method to deliver the biologically activematerial directly to a particular part of the body.

SUMMARY OF THE INVENTION

[0008] These and other objects are accomplished by the presentinvention. To achieve the aforementioned objectives, we have invented animplantable stent prosthesis with channels and methods for manufacturingthe same.

[0009] The implantable stent prosthesis of the present inventioncomprises a sidewall and at least one channel for containing abiologically active material, wherein the sidewall comprises at least inpart a plurality of struts having an exterior surface.

[0010] The present invention also includes a method for making suchimplantable stent prosthesis. In an embodiment, at least one tube ormandrel is placed in contact with a covering material on a stent. Thetube or mandrel is surrounded by the covering material, and then achannel is formed so that it is located within the covering material andwherein the channel has two open ends.

[0011] In another embodiment, a tube or mandrel is covered with achannel material. The covered tube or mandrel is exposed to either heattreatment, chemical treatment or treatment with an adhesive, to form achannel having two open ends. The channel is attached to a sidewall of astent.

[0012] Further, in another embodiment, a tube or mandrel is covered witha channel material. The covered tube or mandrel is exposed to eitherheat treatment, chemical treatment or treatment with an adhesive, toform a channel having two open ends. The channel is attached to a strutmaterial to form a stent wire. The stent wire is woven to form thesidewall of the stent.

[0013] The present invention also includes a method of treating anafflicted area of a surface of a body lumen by implanting the stentprosthesis containing a biologically active material. The biologicallyactive material is delivered to the afflicted area.

DESCRIPTION OF THE DRAWINGS

[0014]FIGS. 1A, 1B, 1C and 1D show embodiments of a stent with channelfor containing a biologically active material where the stent coveringmaterial forms the channel wall defining the channel. FIG. 1A shows across-sectional view of such an embodiment. In the embodiment, an end ofthe outer (first) cover is folded to form the channel, i.e., the channelis formed between two layers of covering material. FIG. 1B depicts across-sectional view of another embodiment of the invention where amiddle portion of the outer stent covering is used to form the channelwall. FIG. 1C depicts a cross-sectional view of an embodiment of theinvention where an inner (second) covering is used to form the channelwall. FIG. 1D depicts a cross-sectional view of an embodiment of theinvention which is similar to that of FIG. 1B. In FIG. 1B, the channelwall is formed by the outer cover in its entirety. On the other hand,the channel wall in FIG. 1D is formed by the outer cover in part and bythe stent sidewall in part.

[0015]FIG. 2 depicts a perspective view of another embodiment of a stentwith a channel positioned along a circumference of the stent.

[0016]FIGS. 3A and 3B illustrate perspective views of embodiments of astent of the invention wherein a channel is woven with the struts orwires of a stent.

[0017]FIG. 4A illustrates a stent wherein a channel is fused to thestent struts. FIG. 4B is a cross-sectional view at the line D in FIG. 4Aof the stent strut and the channel.

[0018]FIG. 5 depicts a cross sectional view of a channel and positionedbetween two layers of a stent covering.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] An embodiment of the present invention is illustrated in FIG. 1A.FIG. 1A shows a stent 10 having a sidewall 16, made up of a plurality ofstruts 13. In the embodiment, an exterior surface of the stent sidewall16 is covered with a first stent covering 12, and an interior luminalsurface of the stent sidewall 16 is covered with a second stent covering14. In this embodiment, the channel is formed by folding one end of thefirst stent covering 12 to form a channel 15. In this case, the channelwall 15 a, which encompasses the space in the channel 15, is formed ofthe covering material. The term “channel” refers to a tube-like pocketalong with the channel wall defining such pocket or space, i.e., thechannel comprises both the channel wall and the pocket defined by thechannel wall. In this embodiment, the channel 15 is positioned along thelongitudinal axis of the stent. When the stent is introduced into a bodylumen, the channel 15 contains biologically active material, and bothends of the channel 15 are preferably sealed.

[0020] The stent 10 may be prepared by the following steps:

[0021] (1) A stent is manufactured by a method known in the art and astent covering 12 is disposed about the exterior surface of the stentsidewall 16.

[0022] (2) A tube or tube-like object having the desired diameter orwidth or shape is placed on top of the exterior surface of the stentcovering near the end of the covering. The covering is then foldedaround or made to surround the tube, so that an end of the tubeprotrudes from a first end of the channel 15.

[0023] (3) The folded cover is treated by heat or chemical treatment oran adhesive or other method known in the art to form a channel 15 havinga channel wall 15 a made of the covering material. At this point, thesecond end of the channel 15 can be sealed by heat-fusing or adhesive orother method known in the art.

[0024] (4) A biologically active material can be placed into the channel15 by injection or other appropriate means known to the skilled artisan.Preferably, the biologically active material is placed into the channel15 at the first end of the channel as the tube is being removed. Thenthe first end of the channel 15 can also be sealed.

[0025] The last step, placement of a biologically active material intothe channel, is not necessarily conducted by a manufacturer but can bedone by a user of the devices just prior to implantation. Thus, thestent of the present invention includes a stent with a channel, whereonly one end is sealed or both ends are open, without any biologicallyactive material contained in the channel. The user would then place abiologically active material into the channel, right before insertion ofthe stent into a body lumen.

[0026] A mandrel can be used to form the channel instead of a tube.Preferably, the mandrel is made of a material which is easilydissolvable in a solvent. When the mandrel is soluble in water or anorganic solvent, it can be removed from the channel by dipping thechannel containing the mandrel and dissolving the mandrel in water orsolvent. Also, the mandrel can contain the biologically active material,and in that case there is no need to remove the mandrel from the channeland no need to later fill the channel with a biologically activematerial. The mandrel can also be made of a material that is insoluble,such as a plastic or metal, and can be removed leaving the open channel.

[0027] Also the channel 15 need not be positioned near the end of thecovering and can be positioned in the middle of the first covering 12 asshown in FIG. 1B. In this case, a tube or mandrel is positioned betweenthe stent sidewall 16 and the first covering 12 as shown in FIG. 1B.Also, as shown in FIG. 1C, the channel 15 can be made from the second,inner, stent covering 14 in the same way as explained above with respectto the first stent covering 12. Moreover, the channel 15 can be formedby the coverings 12, 14 in part and the stent sidewall 16 in part asshown in FIG. 1D.

[0028] Another embodiment of the invention is illustrated in FIG. 2. Inthis embodiment, the channel 26 is positioned along a circumference ofthe stent 20 having a sidewall 27 comprising a plurality of struts 23.Such channel 26 can be made in the same way as explained above, i.e., byinserting a tube or mandrel between the stent sidewall 27 the firststent covering 22 or between layers of the stent covering and thenplacing the first stent covering 22 material around the tube or mandrel,to form a channel 26. The covering surrounding the tube or mandrel canbe treated by heat, chemical or adhesive to form the channel 26. One endof the tube or mandrel may be left protruding from a first open end ofthe channel 26 and second open end of the channel 26 is sealed by anappropriate means, such as by heat or chemical treatment or byadhesives. Then, a biologically active material is placed into thechannel 26 at the first open end. The tube or mandrel is taken out ofthe channel 26, and the first end of the channel 26 can be sealed.Likewise, the channel 26 can be positioned about the outer surface orinner luminal surface of the stent sidewall 27 in a spiral-like manner.

[0029] In addition, besides being formed of a stent covering material,channels 15, 26 may be formed from a layer of a channel material. First,a channel 15, 26 is prepared by wrapping a tube or mandrel with a layerof channel material, i.e., the channel wall is formed of the channelmaterial. More than one layer can be used. These layers need not be ofthe same type of material. The types of materials used for the layerscan be selected to affect the release rate of the biologically activematerials. The channel 15, 26 is positioned in the stent coveringmaterial and attached or fused to the covering material by heat orchemical treatment or by using an adhesive. A material used for formingthe channel can be the same as or different from the material for thestent coverings 2, 14, 22, 24.

[0030] Also, channel 34 made from the channel material can be used toform the stent sidewall. In FIGS. 3A and 3B, the channel 34 is producedseparately, and then woven with the struts 32 to form the stentsidewall. Alternatively, the channel 34 can be woven into aprefabricated stent 30A, 30B comprising struts 32. In FIG. 3A, thechannel 34 is woven into the stent 30A along the stents longitudinalaxis. In FIG. 3B, the channel 34 is woven into the stent 30B along acircumference of the stent 30B. The channel 34 can also be woven inother configurations, such as in a spiral manner. These stents havingsidewalls comprising channels woven with the stent struts can be coveredwith a covering material (not shown). The biologically active materialcan be placed into the channel before or after the channel is woven intothe stent.

[0031]FIG. 4A illustrates another embodiment of the invention wherein apiece stent strut material 43 and a channel 46 are combined or fusedtogether to form a stent wire 42. These wires are used to form thesidewall of the stent 40. The stent may also be coated with a coveringmaterial (not shown in FIG. 4A). FIG. 4B shows a cross-sectional view ofsuch a stent wire 42 comprising strut material 43 and a channel 46coated together with a covering material 48. Either the entire stentsidewall or a part thereof can be made up of such stent wires 42. Thecovering material may be placed over the strut material 43 and channel46 before or after they are used to make the stent sidewall.

[0032] One of the methods for producing the stent 40 comprises thefollowing steps: forming a channel 46 by wrapping a tube or mandrel 47with a channel wall material and fusing the channel 46 to the strutmaterial 43. The channel 46 and strut material are coated with acovering material 48. As the tube or mandrel 47 is removed, abiologically active material is placed into the channel 46 and both endsof the channel can be sealed by an appropriate means, such as withchemical treatment or by heat. The coated stent wire 42 is woven intothe stent 40. The order of the steps is totally interchangeable. Forexample, the coating step is not necessarily before the weaving step.Also, the step of placing the biologically active material can be doneafter the weaving step. The biologically active material can beintroduced into the channel by diffusion in a solution/vapor ormigration. Also, in another embodiment, a channel made of a channelmaterial can be fused to the struts of a prefabricated stent.

[0033] In FIG. 5, a channel 57 is inserted between two layers 52 and 53of a stent covering material. The channel 56 containing a tube ormandrel 57 may be separately prepared from a layer of channel materialand inserted into the two covers 52 and 53 which are covering a stent.Alternatively, a stent cover 50 wherein two cover layers 52 and 53 aresandwiching a channel 56 is formed first, and then the cover 50 may beplaced onto a stent.

[0034] If the material for the channel cannot withstand the heat orother treatment used for processing the stent covering, the channel maybe formed separately from a channel material and then inserted intoanother channel which is formed with the stent covering material asexplained above.

[0035] In another embodiment of the present invention, the tent-likespace formed between (a) stent cover layer(s) and a stent strut can beused as a channel for containing a biologically active material. Thetent-like space can be enlarged by inserting a tube of desired diameterinto it.

[0036] A stent can have more than one channel. Each channel can be madeof an identical material or different materials and also by an identicalmethod or different methods.

[0037] The following is a more detailed description of suitablematerials and method useful in producing a stent with channel(s) of theinvention.

[0038] The term “biologically active material” encompasses therapeuticagents, such as drugs, and also genetic materials and biologicalmaterials. The genetic materials mean DNA or RNA, including, withoutlimitation, of DNA/RNA encoding a useful protein stated below, intendedto be inserted into a human body including viral vectors and non-viralvectors. Viral vectors include adenoviruses, gutted adenoviruses,adeno-associated virus, retroviruses, alpha virus (Semliki Forest,Sindbis, etc.), lentiviruses, herpes simplex virus, ex vivo modifiedcells (e.g., stem cells, fibroblasts, myoblasts, satellite cells,pericytes, cardiomyocytes, sketetal myocytes, macrophage), replicationcompetent viruses (e.g., ONYX-015), and hybrid vectors. Non-viralvectors include artificial chromosomes and mini-chromosomes, plasmid DNAvectors (e.g., pCOR), cationic polymers (e.g., polyethyleneimine,polyethyleneimine (PEI)) graft copolymers (e.g., polyether-PEI andpolyethylene oxide-PEI), neutral polymers PVP, SP1017 (SUPRATEK), lipidsor lipoplexes, nanoparticles and microparticles with and withouttargeting sequences such as the protein transduction domain (PTD). Thebiological materials include cells, yeasts, bacteria, proteins,peptides, cytokines and hormones. Examples for peptides and proteinsinclude growth factors (FGF, FGF-1, FGF-2, VEGF, Endotherial MitogenicGrowth Factors, and epidermal growth factors, transforming growth factorα and β, platelet derived endothelial growth factor, platelet derivedgrowth factor, tumor necrosis factor α, hepatocyte growth factor andinsulin like growth factor ), transcription factors, proteinkinases, CDinhibitors, thymidine kinase, and bone morphogenic proteins (BMP's),such as BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8.BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.Currently preferred BMP's are BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7.These dimeric proteins can be provided as homodimers, heterodimers, orcombinations thereof, alone or together with other molecules. Cells canbe of human origin (autologous or allogeneic) or from an animal source(xenogeneic), genetically engineered, if desired, to deliver proteins ofinterest at the transplant site. The delivery media can be formulated asneeded to maintain cell function and viability. Cells include whole bonemarrow, bone marrow derived mono-nuclear cells, progenitor cells (e.g.,endothelial progentitor cells) stem cells (e.g., mesenchymal,hematopoietic, neuronal), pluripotent stem cells, fibroblasts,macrophage, and satellite cells.

[0039] Biologically active material also includes non-genetictherapeutic agents, such as:

[0040] anti-thrombogenic agents such as heparin, heparin derivatives,urokinase, and PPack (dextrophenylalanine proline argininechloromethylketone);

[0041] anti-proliferative agents such as enoxaprin, angiopeptin, ormonoclonal antibodies capable of blocking smooth muscle cellproliferation, hirudin, and acetylsalicylic acid, amlodipine anddoxazosin;

[0042] anti-inflammatory agents such as glucocorticoids, betamethasone,dexamethasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazine, and mesalamine;

[0043] antineoplastic/antiproliferative/anti-miotic agents such aspaclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine,epothilones, methotrexate, azathioprine, adriamycin and mutamycin;endostatin, angiostatin and thymidine kinase inhibitors, taxol and itsanalogs or derivatives;

[0044] anesthetic agents such as lidocaine, bupivacaine, andropivacaine;

[0045] anti-coagulants such as D-Phe-Pro-Arg chloromethyl keton, an RGDpeptide-containing compound, heparin, antithrombin compounds, plateletreceptor antagonists, anti-thrombin anticodies, anti-platelet receptorantibodies, aspirin (aspirin is also classified as an analgesic,antipyretic and anti-inflammatory drug), dipyridamole, protamine,hirudin, prostaglandin inhibitors, platelet inhibitors and tickantiplatelet peptides;

[0046] vascular cell growth promotors such as growth factors, VascularEndothelial Growth Factors (FEGF, all types including VEGF-2), growthfactor receptors, transcriptional activators, and translationalpromotors;

[0047] vascular cell growth inhibitors such as antiproliferative agents,growth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin;

[0048] cholesterol-lowering agents; vasodilating agents; and agentswhich interfere with endogenous vasoactive mechanisms;

[0049] anti-oxidants, such as probucol;

[0050] antibiotic agents, such as penicillin, cefoxitin, oxacillin,tobranycin

[0051] angiogenic substances, such as acidic and basic fibrobrast growthfactors, estrogen including estradiol (E2), estriol (E3) and 17-BetaEstradiol; and

[0052] drugs for heart failure, such as digoxin, beta-blockers,angiotensin-converting enzyme (ACE) inhibitors including captopril andenalopril.

[0053] A biologically active material can be placed into the channel byvarious methods including injection as explained above. For instance,after the biologically active material is dissolved or suspended inwater or an aqueous solution, it can be injected into the channel. Also,the biologically active material can be introduced into a channel bydiffusion in the solution. For example, a stent with an empty channel isdipped in a solution or suspensions of the biologically active materialto allow the biologically active material to diffuse into the channel.Also, when the biologically active material is dissolved in an organicsolvent, it can be introduced into a channel by diffusion in a vapor ofthe solvent solution. When the biologically active material is abiological material, such as tissue culture cells, yeast, and bacteria,it can be introduced into a channel by migration or by injection of aculture medium containing the biological material.

[0054] Stents suitable for the present invention include any stent formedical purpose without limitation, which are known to the skilledartisan. Stents suitable for the present invention include vascularstents such as self-expanding stents and balloon expandable stents.Examples of self-expanding stents useful in the present invention areillustrated in U.S. Pat. Nos. 4,655,771 and 4,954,126 issued to Wallstenand U.S. Pat. No. 5,061,275 issued to Wallsten et al. Examples ofappropriate balloon-expandable stents are shown in U.S. Pat. No.4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturcoand U.S. Pat. No. 4,886,062 issued to Wiktor. Expandable stent may beformed from polymeric, metallic and/or ceramic materials. Suitablematerials include, without limitation, metals, such as tantalum,stainless steel, nitinol, titanium, and alloys, and polymeric materials,such as poly-L-lactic acid, polycarbonate, and polyethyleneterephtalate. Also, stents made with biostable or bioabsorbable polymerssuch as poly(ethylene terephthalate), polyacetal, poly(lactic acid),poly(ethylene oxide)/poly(butylene terephthalate) copolymer could beused in the present invention.

[0055] Stent covering materials suitable for the present inventioninclude any covering material for the stent which are known to theskilled artisan. The covering can be a polymer, which is preferablyselected from elastomeric polymers, e.g., silicones, polyurethanes,thermoplastic elastomers, ethylene vinyl acetate copolymers, polyolefinelastomers, EPDM rubbers, polytetrafluoroethylene (PTFE) or expandedPTFE (ePTFE).

[0056] Suitable thickness of the cover are known in the art and can beselected by artisans. The cover can be produced by any method suitableand known in the art. For example, by dipping a stent in a polymer,spraying a polymer covering solution onto a stent, wrapping the stentwith a material or encapsulating the stent in a polymer tube.

[0057] Examples for suitable materials for making the channel, i.e.,channel materials, are, without limitation, poly(L-lactic acid),poly(lactic acid-co-glycotic acid), polyether, polyurethane, andsilicone. The material for the channel material can be selected tocontrol release of the drug contained in the channel. For example, inthe embodiment where the channel is located in the stent covering, thechannel material and covering materials used are selected so that thebiologically active material can be released at a certain rate or in acertain manner.

[0058] Preferably, the channel has a cylindrical-like shape, where thechannel has a circular cross-section as shown in the figures. However,the channel need not be cylindrical. Instead, the channel can have anoblong, square or star-like shaped cross-section, or any other type ofshape.

[0059] The diameter of the channel of the present invention is notlimited and should be selected depending on the type and amount ofbiologically active material to be deliver, the rate of the delivery,and the method for manufacture. For instance, when the biologicallyactive material is injected into the channel by a syringe rather than bydiffusion, migration or by inserting a mandrel containing thebiologically active material, the channel diameter should be largeenough to allow such injection. When the biologically active material isplaced into the channel by migration, the channel should haveopening(s), i.e., an open end or pore(s) which are large enough for suchmigration of the biologically active material into and out of thechannel space. Alternatively, the biological material can be trapped inthe channel and prevented from migration but allowed to produce abiological active material that can actively regulate biologicalfunction. For example, growth-factor producing cells are trapped in thechannel, but the growth factor that these cells produce is graduallyreleased from the channel while the cells stay in the channel. Moreover,the present invention may include not only macro channels but also microchannels. The micro channels may be produced by micro-fabrication, byprinting a pattern on the stent or stent cover, or using pre-printedsheets. The macro channels maybe preferable because of their largercapacity for containing biologically active material.

[0060] The suitable diameter of the channel depends on various factors,such as the material to be used to make the channel, the manner toinject the biologically active material, the thickness of the material,the size and type of the stent, the configuration of the channel, methodof manufacture, amount of the biologically active material to be deliverand the rate of the delivery. The inner diameter of the channel isnormally from about 10 μm to about 1 mm, preferably from about 50 μm toabout 500 μm.

[0061] The thickness of the channel wall is not limited and depends onthe biologically active material to be deliver, the rate of thedelivery, method for manufacture, and type of channel material used. Forexample, when the channel material is poly(ethylene terephthalate), thethickness is generally between 10 μm and 2000 μm, preferably between 50μm and 600 μm, more preferably 50 μm and 450 μm.

[0062] The release rate of the biologically active material depends onthe degree of porosity of the channel material and covering material,hydrophobicity of the channel material and covering material, thethickness of the channel wall and covering, and the biologically activematerial's chemical and physical features. Thus, by selecting anappropriate covering material, channel material and a thickness of thecovering and/or channel wall, the release rate of a biologically activematerial can be controlled.

[0063] Additionally, a further control can be possible by using widevariety of pharmaceutical forms of the drugs and carriers, such as bars,particles, gels, and fluids.

[0064] The release rate of the biologically active material is notnecessarily uniform. For example, by selecting a porous material forinner covering of stent and a less porous material for the outercovering, the release rate of the biologically active material at theinterior luminal surface of the stent is greater than at the stent'sexterior surface. Accordingly, there can be a lag time between theimplantation of the stent and the biologically active material is firstreleased. Alternatively, there can be a gradient for a biologicallyactive material contained in the channel. If the concentration of thebiologically active material is high in the center of the channel andbecomes lower at points further from the center, the release rate canincrease with time. If the concentration of the biologically activematerial is low in the center of the channel and becomes higher asdistant from the center, the releasing rate can gradually decrease withtime.

[0065] In some embodiments, the channel wall has a plurality of portswhich allow a biologically active material to pass through. Thebiologically active material, such as tissue culture cells, yeast,bacteria can migrate through the ports. Such channel may besubstantially covered with a covering.

[0066] A stent of the present invention can be implanted into a bodylumen using any conventional method known in the art. The body lumeninto which the stent can be implanted includes blood vessels, urinarytract, coronary vasculature, esophagus, trachea, colon, and biliarytract. Once the stent with the channel(s) is placed in a body lumen, thebiologically active material in the channel can be released from thechannel by diffusion through the channel wall. In another embodiment ofthe present invention, a biologically active material is released fromthe channel by application of pressure. For example, the stent isinserted into a body lumen by a balloon catheter and the biologicallyactive material is squeezed out from the channel when the stent ispressed onto the body lumen surface by expanding balloon.

[0067] The description contained herein is for purposes of illustrationand not for purposes of limitation. Changes and modifications may bemade to the embodiments of the description and still be within the scopeof the invention. Furthermore, obvious changes, modifications orvariations will occur to those skilled in the art. Also, all referencescited above are incorporated herein, in their entirety, for all purposesrelated to this disclosure.

We claim:
 1. A method for making an implantable stent prosthesis havinga sidewall comprised of a plurality of struts and at least one channelcomprising a channel wall defining a channel space for containing abiologically active material, the method comprises the steps of: (a)covering a tube or mandrel with a channel material; (b) forming thechannel, having two open ends, by exposing the covered tube or mandrelto a treatment selected from heat treatment, chemical treatment ortreatment with an adhesive; and (c) attaching the channel to thesidewall.
 2. The method of claim 1, wherein the channel is attached tothe sidewall by attaching the channel to a strut.
 3. The method of claim2, wherein the channel is attached to the strut by fusing the channel tothe strut.
 4. The method of claim 2, wherein the channel is attached tothe sidewall by weaving the channel with a strut.
 5. The method of claim2, which further comprises covering the channel and strut with acovering material.
 6. The method of claim 1, which further comprisesremoving the tube or mandrel and introducing the biologically activematerial into the channel.
 7. The method of claim 6, wherein the tube ormandrel is removed before the channel is attached to the sidewall. 8.The method of claim 6, wherein the biologically active material isintroduced into the channel before the channel is attached to thesidewall.
 9. The method of claim 6, wherein the biologically activematerial is introduced into the channel using a technique selected frominjecting the biologically active material into the channel, allowingthe biologically active material to diffuse into the channel or allowingthe biologically active material to migrate into the channel.
 10. Themethod of claim 1, wherein the channel material is selected frompoly(L-lactic acid), poly(lactic acid-co-glycotic acid), polyether,polyurethane, or silicone.
 11. A method for making an implantable stentprosthesis having a sidewall comprised of (1) a plurality of strutsformed from a strut material and (2) at least one channel comprising achannel wall defining a channel space for containing a biologicallyactive material, the method comprises the steps of: (a) covering a tubeor mandrel with a channel material; (b) forming the channel by exposingthe covered tube or mandrel to a treatment selected from heat treatment,chemical treatment, or treatment with an adhesive; (c) attaching thechannel to strut material to form a stent wire; and (d) weaving thestent wire to form the sidewall of the stent.
 12. The method of claim 11wherein the stent wire is covered with a covering material.
 13. Themethod of claim 12 wherein the covering material is selected fromsilicones, polyurethanes, thermoplastic elastomers, ethylene vinylacetate copolymers, polyolefin elastomers, EPDM rubbers,polytetrafluoroethylene or expanded polytetrafluoroethylene.
 14. Themethod of claim 12 wherein the stent wire is covered with the coveringmaterial before the stent wire is woven.